The health of approximately half of the U.S. population continues to be negatively impacted by air[unreadable] pollutants such as ozone (O3), the major oxidant pollutant in photochemical smog. Recent epidemiologic[unreadable] studies suggest that exposure to ambient O3 induces long-term impairments to the pulmonary function of[unreadable] children. The toxicological mechanisms of O3-related airway injury and how age and exposure history[unreadable] govern the child's susceptibility to O3-induced airway injury remain poorly understood. Exposure to O3 is[unreadable] also known to cause injury not only to the lungs, but also to the nose. The overall goal of Project 3 is to[unreadable] determine the nature and distribution of airway injury, adaptation and repair in the nasal passages of infant[unreadable] monkeys and rats episodically exposed to O3. Intranasal distribution and severity of the O3-induced lesions[unreadable] will be determined by image analysis and morphometric techniques. The O3-induced nasal alterations will[unreadable] be compared to biochemical changes in intracellular and extracellular antioxidants present in the nasal[unreadable] mucosa and extracellular airway lining fluid, respectively. The identified, site-specific alterations in mucosal[unreadable] morphology and in regional tissue/fluid biochemistry caused by episodic O3 exposures will also be[unreadable] compared to computer-assisted estimates of intranasal, regional dosimetry of O3. The site-specific[unreadable] comparisons throughout the nasal passages will be used to determine how tissue susceptibility and airflowdriven[unreadable] dosimetry contribute to the pathogenesis of nasal injury and remodeling caused by acute and[unreadable] chronic O3 exposures. The results of these studies will provide a better understanding of how episodic O3[unreadable] exposure affects the growth and development of the nasal airways at the macroscopic, microscopic and[unreadable] molecular levels. Our underlying premise is that the developing nasal mucosa in infant animals is more[unreadable] susceptible to the toxic effects of O3 than is the fully developed nasal mucosa of adults. We hypothesize[unreadable] that this disparity in mucosal responses is due to differences between infants and adults in the regulation of[unreadable] ceNular and extracellular antioxidants in the nasal airways. Project 3 is also designed to test the hypothesis[unreadable] that O3-induced morphologic, biochemical, and molecular responses in the nose are sentinels for O3-[unreadable] induced alterations in the lung. Furthermore, this project is designed to test the hypothesis that the[unreadable] episodic nature of the environmental exposure to O3 permanently alters the developing nasal airway[unreadable] making it more vulnerable, later in life, to adverse alterations from subsequent exposures to inhaled[unreadable] toxicants (e.g., ozone and bacterial endotoxin). Our project will rely heavily on projects 1, 2 and 4 to[unreadable] accomplish the proposed investigations. Our research will provide important information that is crucial for[unreadable] understanding the potential, long-term health effects of air pollution on the developing airways of children.